Dihydrotestosterone sensitises LNCaP cells to death induced by epigallocatechin-3-Gallate (EGCG) or an IGF-I receptor inhibitor.
BACKGROUND
Compelling evidence has accumulated for chemopreventive effects for the active component of green tea Epigallocatechin-3-Gallate (EGCG) particularly for prostate cancer (CaP).


METHODS
We have assessed interactions between the effects of EGCG and two main regulators of prostate cell function, dihydrotestosterone (DHT) and insulin-like growth factor-1 (IGF-I). Using LNCaP (androgen-sensitive), PC3 and DU145 (androgen-resistant) CaP cell lines, we assessed the effect of EGCG alone on growth (0-200 microM) and on cell death (0-50 microM).


RESULTS
EGCG decreased the proliferation of all the CaP cancer cells in a dose-dependent manner with an increase in apoptosis from 30 to 50 microM. With DU145 cells, a sub-apoptotic dose of EGCG (10-20 microM) reduced IGF-induced growth. With LNCaP cells, a sub-apoptotic dose of EGCG (8 microM) switched DHT from a growth promoter to a growth inhibitor. A similar reversal of DHT effect was seen in the presence of an IGF-I receptor inhibitor, AG1024 (1 microM). These responses appeared to be due to DHT sensitizing the cells to apoptosis by EGCG and AG1024 (P < 0.01 and P < 0.001 respectively).


CONCLUSIONS
Our data suggests that both green tea and AG1024 are effective in inhibiting cell growth and inducing death in CaP cells but the effects of both are more effective in the presence of androgen.
Thomas
Francis
F
IGF & Metabolic Endocrinology Group, Department of Clinical Sciences North Bristol, The Medical School Unit, Southmead Hospital, Bristol, UK.
Patel
Suril
S
Holly
Jeff M P
JM
Persad
Raj
R
Bahl
Amit
A
Perks
Claire M
CM
D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000502:physiology; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000235:genetics; D013196:Dihydrotestosterone / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000302:isolation & purification; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D013196:Dihydrotestosterone; D002392:Catechin; D017526:Receptor, IGF Type 1; C057580:gallocatechol; D013936:Thymidine